Evidence of histone modification affecting ARID1A expression in colorectal cancer cell lines.

ABSTRACT

Aim: The current study aimed to focus on the role of histone deacetylation in reduced ARID1A expression in colorectal cancer cell lines. Background: ARID1A, a subunit of the switch/sucrose nonfermentable chromatin remodeling complex, has emerged as a bona fide tumor suppressor and is frequently downregulated and inactivated in multiple human cancers. Epigenetic modifications play an important role in dysregulation of gene expression in cancer. DNA methylation has been reported as an important regulator of ARID1A expression in colorectal cancer cell lines; however, the histone modification role in ARID1A suppression in colorectal cancer remains unclear. Methods: The expression levels of ARID1A mRNA were determined using real-time quantitative PCR in colorectal cancer cell lines including HCT116, SW48, HT29, SW742, LS180, and SW480. To evaluate the effect of histone deacetylation on ARID1A expression, all cell lines were treated with trichostatin A (TSA), a histone deacetylase inhibitor. SPSS software (Version 23) and GraphPad Prism (Version 6.01) were applied for data analysis using one-way ANOVA, followed by Tukey's multiple comparison tests. Results: Treatment of colorectal cancer cell lines with TSA increased ARID1A expression in a cell line-dependent manner, suggesting that histone deacetylation is at least one factor contributing to ARID1A downregulation in colorectal cancer. Conclusion: Histone deacetylase inhibitors might provide a strategy to restore ARID1A expression and may bring benefits to the colorectal cancer patients with a broader range of genetic backgrounds.